Applicator for water-soluble sheet-shaped preparation

ABSTRACT

To provide a means which makes it possible to reliably administer a sheet-like water-soluble preparation to skins at various sites and supply water from a back side of the sheet-like water-soluble preparation. 
     A nozzle having at least one hole on an end portion having a plane with a size capable of holding a sheet-like water-soluble preparation, and having concave-convex portions on a portion of the plane excluding the hole; and an applicator for a sheet-like water-soluble preparation, which is composed of a liquid container and the nozzle.

TECHNICAL FIELD

The present invention relates to an applicator nozzle for applying asheet-like water soluble preparation to a skin, and an applicatorequipped with the nozzle.

BACKGROUND ART

As a method of administering a drug to a human body, oral administrationand transdermal administration are often used. Although injection is atypical transdermal administration method, it is troublesome andpainful. In transdermal administration, skin stratum corneum works as abarrier to drug permeation, so only applying the drug on a skin surfacedoes not necessarily cause enough permeability. In contrast, perforationof the corneum by using a minute needle, i.e. a microneedle canremarkably improve drug permeation efficiency compared to theapplication method. An article in which a large number of themicroneedles are integrated on a substrate is a microneedle array.Furthermore, a product in which sheets such as an adhesive sheet foradhering the microneedle array to a skin or a protective release sheetfor protecting and supporting the adhesive sheet when applying themicroneedle array to a skin are added to the microneedle array in orderto facilitate its use is called a microneedle patch.

When administering a microneedle array to a skin, it is not easy toinsert microneedles into the skin only by pressing the microneedle arraywith a finger. This is because the skin is generally a soft and elastictissue, and thus even if the pointed tips of the microneedles arepressed against the skin, the skin absorbs the impact and deforms toprevent the microneedles from entering the skin.

It is appropriate to impact the microneedle array in a direction to theskin for administering the microneedle array to the impact-absorbableskin. As specific methods for administering the microneedle array,microneedle administration devices (microneedle applicator) using aspring (Patent Documents 1 to 6, and 8), an air pressure (PatentDocument 5), a magnetic force (Patent Document 7), and the like, havebeen proposed so far. For facilitating use of a spring even for womenand children, ingenuity is required for a spring compression method anda trigger method. In addition, it is not necessarily easy to use the airpressure and the magnetic force. The conventional microneedle arrayadministration devices still have practical problems, and the users havedemanded a simpler device which can achieve reliable insertion.

Although microneedles made of a water-soluble material dissolve in waterin a skin after insertion, this dissolution takes a lot of time and thusremarkably impairs convenience for recipients particularly in a casethat the microneedles are intended for cosmetics. A microneedle array isprepared using a water-soluble material and inserted into a skin, towhich subsequently water is supplied from the back side of themicroneedle, and then the microneedles rapidly dissolve (Patent Document9). In addition, the present inventors have developed a cosmetichyaluronic acid gel sheet composed of a water-soluble polymer hyaluronicacid as a raw material, and have reported that the sheet is applied to askin, to which subsequently a small amount of water is added, and theskin is massaged to enhance permeation of the hyaluronic acid andingredients to the skin (Patent Document 10).

PRIOR ART DOCUMENTS

Patent Document 1: Japanese Unexamined Patent Application No.2004-510530 (Japanese Patent No. 4198985)

Patent Document 2: Japanese Unexamined Patent Application No.2004-510534 (Japanese Patent No. 4104975)

Patent Document 3: Japanese Unexamined Patent Application No 2004-510535(Japanese Patent No. 4659332)

Patent Document 4: Japanese Unexamined Patent Application No.2005-533625

Patent Document 5: Japanese Unexamined Patent Application No.2006-500973

Patent Document 6: Japanese Unexamined Patent Application No.2007-509706 (Japanese Patent No. 4682144)

Patent Document 7: Japanese Patent Application Laid-Open No. 2011-078711

Patent Document 8: Japanese Patent Application Laid-Open No. 2014-42788

Patent Document 9: Japanese Patent Application Laid-Open No. 2011-194189(Japanese Patent No. 5408592)

Patent Document 10: Japanese Patent Application Laid-Open No.2014-024828 (Japanese Patent No. 5840107)

SUMMARY OF INVENTION Problem to be Solved

The microneedle array and the cosmetic gel sheet composed of awater-soluble polymer as a raw material are sheet-like flexiblepreparations having a thickness of about several hundred μm forimproving adhesiveness to a skin. When such a sheet-like water-solublepreparation is applied to the skin, the preparation absorbs moisture ona fingertip and adheres to the finger rather than the target skin, orwhen the preparation is applied to a scalp, adhesiveness is inhibited byhairs, and thus the preparation peels off before absorbed from thescalp, in some cases.

The problem to be solved by the present invention is to provide a meanswhich makes it possible to reliably administer a sheet-likewater-soluble preparation to skins at various sites and supply waterfrom a back side of the sheet-like water-soluble preparation.

Herein, the sheet-like water-soluble preparation in the presentinvention includes not only a microneedle array but also a sheet-likepreparation like a cosmetic water-soluble gel sheet, intended to berapidly dissolved in water after application to the skin andpercutaneously absorbed. The sheet-like water-soluble preparation isprepared using a water-soluble polymer as a base and has a thickness ofabout 1 mm or less. Examples of the water-soluble polymer includehyaluronic acid (or a sodium salt thereof) and a derivative thereof,collagen, hydroxypropylcellulose, chondroitin sulfate, dextran,proteoglycan, etc. and a mixture thereof. The back side of thesheet-like water-soluble preparation refers to a side opposite to theside in close contact with the skin.

Solution to Problem

The present inventors have conducted extensive studies in order to solvethe above problem, and as a result, they have succeeded in developing anozzle which facilitates adhesion and detachment of the sheet-likewater-soluble preparation. Furthermore, the present inventors havecompleted a device which makes it possible to instantly apply thesheet-like water-soluble preparation to a skin and dissolve thepreparation by attaching such a nozzle to various liquid containers.

The present invention is as follows.

[1] A nozzle having at least one hole on an end portion having a planewith a size capable of holding a sheet-like water-soluble preparation,and having concave-convex portions on a portion of the plane excludingthe hole.[2] The nozzle according to [1], wherein a depth of the concave-convexportions is 0.1 to 3.0 mm.[3] The nozzle according to [1] or [2], wherein the concave-convexportions form grooves extending from the hole toward a peripheral edgeof the end portion.[4] The nozzle according to any one of [1] to [3], wherein theperipheral edge of the end portion is surrounded by a convex portionhigher than the concave-convex portions.[5] The nozzle according to any one of [1] to [4], which is made of asynthetic resin selected from a group consisting of a polyethyleneresin, a polypropylene resin, a polyurethane resin, a polyvinylchloride, and a silicone resin.[6] An applicator for a sheet-like water-soluble preparation, which iscomposed of a liquid container and the nozzle according to any one of[1] to [5].[7] The applicator according to [6], wherein the nozzle is attached toan opening of the liquid container.[8] The applicator according to [6] or [7], wherein the sheet-likewater-soluble preparation is held on the end portion of the nozzle so asto be applied to the skin, and a liquid is supplied to a back side ofthe preparation by pressing the liquid container.[9] The applicator according to [6], wherein the liquid container isequipped with a spray device, and the nozzle is attached to an endopening of the spray device.[10] The applicator according to [9], wherein the sheet-likewater-soluble preparation is held on the end portion of the nozzle so asto be applied to the skin, and the liquid is supplied to the back sideof the preparation by discharge from the spray device.[11] The applicator according to [6], wherein the liquid container isequipped with a pump, and the nozzle is attached to an end opening ofthe pump.[12] The applicator according to [11], wherein the sheet-likewater-soluble preparation is held on the end portion of the nozzle so asto be applied to the skin, and the liquid is ejected to the back side ofthe preparation by pushing the pump.

EFFECTS OF INVENTION

The nozzle according to the present invention can rapidly dissolve thepreparation by pressing the end of the nozzle against the sheet-likewater-soluble preparation pasted on a skin and supplying water to thepreparation from the hole of the nozzle. Since the end portion of thenozzle according to the present invention has the concave-convexportions, the dissolved preparation reliably stays on the skin sidewithout adhering to the end portion of the nozzle. The end portion ofthe nozzle according to the present invention has the plane having theconcave-convex portions, and thus in a case of a relatively smallsheet-like water-soluble preparation, the preparation can be applied tothe skin while held on the plane of the end portion. This case ishygienic because the preparation is not directly handled with hands.

The applicator according to the present invention is composed of thenozzle according to the present invention and the liquid container, andany liquid container may be used as long as the opening of the liquidcontainer can be fitted into the nozzle. When a water-solublemicroneedle array is administered using the applicator according to thepresent invention, the end of the nozzle is pressed against themicroneedle array and left for an appropriate time to ensure insertionof the microneedles to the skin. Furthermore, the end of the nozzle ispressed against the microneedle array to uniformly supply water from theliquid container to the entire surface of the back side of the array, sothat the microneedle array can rapidly dissolve. When the cosmeticwater-soluble gel sheet is applied using the applicator according to thepresent invention, the end of the nozzle is pressed against the gelsheet, and water in the liquid container is supplied from the back side,so that the gel sheet rapidly dissolves and spreads over the skinsurface to enhance moisture retention of the skin and absorption ofvaluable components.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 illustrates an example of a shape of a nozzle end portion.

FIG. 2 illustrates a sectional view and a bottom view of the nozzle inExample 1.

FIG. 3 illustrates an applicator in which the nozzle in Example 1 isattached to a liquid container made of polyethylene.

FIG. 4 illustrates examples (A, B, C) of the nozzle, wherein each leftside shows a bottom view, and each right side shows a sectional view.

FIG. 5 illustrates other examples (D, E, F) of the nozzle, wherein eachleft side shows a bottom view, and each right side shows a sectionalview.

FIG. 6 illustrates examples (A, B, C) of the applicator in which thenozzle is attached to various liquid containers having openings.

DESCRIPTION OF EMBODIMENTS

The nozzle according to the present invention is a water supply memberintended to dissolve the sheet-like water-soluble preparation. The endportion of the nozzle has the plane with a size capable of holding thesheet-like water-soluble preparation. For the nozzle according to thepresent invention, the shape of the plane of the end portion can bechanged depending on the size of the sheet-like water-solublepreparation, and may be a circle, an oval, a comma shape, a polygon suchas triangle, square, pentagon and hexagon. The main body of the nozzleaccording to the present invention may have a cylinder shape, anelliptic cylinder shape, or a polygonal pillar shape in accordance withthe shape of the plane of the end portion. The cylinder shape isdesirable for fitting the nozzle into openings of various liquidcontainers.

The end portion of the nozzle according to the present invention has atleast one hole. The number of the holes may be two or more for thepurpose of introducing water from the liquid container to the back sideof the sheet-like water-soluble preparation, and also the size of thehole is not particularly limited. The hole may be positioned at thecenter or the peripheral portion of the plane of the end portion. Also,the arrangement and interval of the plurality of holes are notparticularly limited.

The concave-convex portions are formed on the plane of the end portionof the nozzle according to the present invention excluding the holes.The concave-convex portions are of any shapes such as a helical shape, adot shape and a radial shape as long as the sheet-like water-solublepreparation can be attached to or detached from the end portion of thenozzle and grooves capable of supplying water over the entire endportion from the hole can be formed. In relation to the degree of theconcave and convex, typically the concave and convex have depths ofdesirably 0.1 to 3.0 mm, more preferably 0.1 to 2.0 mm. If the depth is0.1 mm or less, the rapidity is impaired in supplying water to thesurface through the hole. If the depth is 3.0 mm or more, the amount ofwater supplied over the entire surface through the hole needs to belarge.

The area ratio of the convex portions or flat portions to the grooveportions or concave portions is desirably 20:1 or higher. If the arearatio of the concave portions is too small, the groove portions aresmall, and it is difficult to supply water over the entire bottomsurface. If the area of the groove portions is too large, the plane ofthe nozzle flat portion is small, and even if the water-soluble sheet ispressed against the skin by the nozzle, the adhesiveness with the flatportion is insufficient, resulting in possibility of insufficientadhesion to the nozzle. Thus, the area ratio of the convex portions orflat portions to the groove portions or concave portions is desirably1:10 or lower.

It is desirable that the peripheral edge of the end portion of thenozzle according to the present invention is surrounded by a convexportion higher than the aforementioned concave-convex portions so thatsupplied water does not overflow. The convex portion on the peripheraledge plays a role of a weir such that water spread through the groovesformed by the concave-convex portions is prevented from overflowing tothe outside of the sheet-like water-soluble preparation.

The nozzle according to the present invention desirably has grooves inwhich the concave-convex portions extend from the hole toward theperipheral edge of the end portion for the purpose of smoothly supplyingan appropriate amount of water to the entire sheet-like water-solublepreparation. Herein, the groove refers to a lower part formed byadjacent two convex portions and one concave portion surrounded by thetwo convex portions. The shape of the groove is not particularlylimited. Specific examples of the grooves include concentrical elongatedgrooves on the concave-convex portions 3 concentrically spreading arounda hole 2 at the center, and radial (flabellate) grooves 5 directlyconnected to the hole 2, on the end portion of the nozzle shown inFIG. 1. This nozzle has a convex portion 4 on the peripheral edge.

FIG. 4 and FIG. 5 illustrate further aspects of the nozzle according tothe present invention. In FIG. 4A and FIG. 4C, the radial grooves 5 andconcentrical grooves are formed. In FIG. 4B, the concave-convex portions3 are formed of many dots, and the grooves 5 made of the dots are formedfrom the hole 2 toward the peripheral edge. In FIG. 5D, helical grooves5 are formed from the hole 2 toward the peripheral edge. In FIG. 5E, alarge hole 2 is formed at the center, and concentrical grooves 5 areformed around the hole 2. In FIG. 5F, fine concave-convex portions 3,which are mesh-like grooves invisible to the naked eye, are formed overthe entire plane excluding the hole 2.

Materials of the nozzle according to the present invention are notparticularly limited, and various materials such as metal, ceramic andplastic can be used. Considering easiness of manufacture, convenience inuse and the like, plastic is preferable, and particularly, a polyolefinresin such as a polyethylene resin and a polypropylene resin, and asynthetic resin such as a polyvinyl chloride, a polyurethane resin and asilicone resin are more preferable. Considering fittability of variousmaterials with the liquid container and goodness in contact feeling ofthe nozzle to the skin, a soft polymer material is preferable. As ameasure for a hardness of the nozzle material, a Young's modulus isdesirably 500 Pa to 5 MPa. As a specific material, a soft polyolefinresin, a polyurethane resin and a silicone resin are preferable, and thesilicone resin is more preferable.

A nozzle made of a synthetic resin can be manufactured by a knownmethod, e.g. a molding method by injecting a raw material resin into amold.

The applicator according to the present invention is composed of aliquid container and the nozzle according to the present invention. Theliquid container and the nozzle may be in a combination in which theyare separated. In this case, the nozzle is attached to the opening ofthe liquid container during use. In the liquid container, a liquid maybe previously charged, or the liquid may be injected immediately beforeuse. In the present invention, the liquid is typically water, but may bea mixture liquid with a solvent other than water as long as thesheet-like water-soluble preparation can be dissolved. In addition, theliquid may be an aqueous solution additionally containing medicinalingredients and valuable ingredients to be applied to the skin asneeded.

The material for the liquid container is not particularly limited, andvarious materials such as metal, ceramic and plastic can be used inconsideration of the fittability with the nozzle. Considering easinessof manufacture, convenience in use, and the like, plastic is preferable,and particularly, a polyolefin resin such as a polyethylene resin and apolypropylene resin, and a synthetic resin such as a polyvinyl chloride,a polyurethane resin and a silicone resin are more preferable.

The applicator according to the present invention has the nozzleaccording to the present invention. The applicator is e.g. an applicatorshown in FIG. 6C. In this case, the sheet-like water-soluble preparationis held on the end portion of the nozzle so as to be applied to theskin, and the liquid can be supplied to a back side of the preparationby pressing the liquid container. The amount of the liquid to besupplied can be appropriately set depending on the size (area,thickness) or the like of the sheet-like water-soluble preparation. Theamount of the liquid can be regulated depending on a size of the hole ofthe nozzle, a pressure applied to the liquid container, a frequency ofpressings, or the like.

When the liquid container is equipped with a spray device, the nozzle isattached to an end opening of the spray device in the applicatoraccording to the present invention. The applicator is e.g. an applicatorshown in FIG. 6B. Also in this case, similarly the sheet-likewater-soluble preparation is held on the end portion of the nozzle so asto be applied to the skin, and the liquid can be supplied to the backside of the preparation by discharge from the spray device. The amountof the liquid to be supplied can be appropriately set depending on thesize (area, thickness) or the like of the sheet-like water-solublepreparation. The amount of the liquid can be regulated depending on asize of the hole of the nozzle, dischargeability of the spray device, afrequency of discharges, or the like.

When the liquid container is equipped with a pump, the nozzle isattached to an end opening of the pump in the applicator according tothe present invention. The applicator is e.g. an applicator shown inFIG. 6A. Also in this case, similarly the sheet-like water-solublepreparation is held on the end portion of the nozzle so as to be appliedto the skin, and the liquid can be ejected to the back side of thepreparation by pushing the pump. The amount of the liquid to be ejectedcan be appropriately set depending on the size (area, thickness) or thelike of the sheet-like water-soluble preparation. The amount of theliquid can be regulated depending on a size of the hole of the nozzle,dischargeability of the pump, a frequency of ejections, or the like.

As described above, in the present invention, various liquid containersare attached with the nozzle according to the present invention in aform that can be fitted into the opening of the liquid container, toprovide various forms of applicators. Thus, the nozzle and the liquidcontainer can be freely combined depending on the shape, the applicationpurpose, the application frequency, the application site, or the like ofthe sheet-like water-soluble preparation. In addition, the nozzleaccording to the present invention can be inexpensively mass-produced,and therefore, for use, the nozzle can be changed for each subject andeach application day. After use, the nozzle is detached from theapplicator, the opening of the applicator is sealed with a cap or thelike, the liquid remaining in the liquid container is stored underrefrigeration, and can be used again within an expiration date.Furthermore, the applicator according to the present invention can alsobe used as a single-use disposable device by attaching the nozzle to theliquid container charged with a single dose of the liquid.

Hereinafter, embodiments of the present invention will be explainedbased on Examples. However, the present invention is not limited tocontents of Examples.

EXAMPLES Example 1

A nozzle as shown in FIG. 1 was prepared. The nozzle was prepared bymold injection using a silicone resin (one liquid type RTV rubber,manufactured by Shin-Etsu Chemical Co., Ltd.). On a plane of a nozzleend 1, a diameter was 12 mm, a depth of concentrical concave-convexportions 3 was 0.5 mm, and an interval between the concave-convexportions was 1 mm. The upper diagram of FIG. 2 shows a sectional view ofthe entire nozzle, and the lower diagram of FIG. 2 shows a bottom viewof the nozzle. The hole 2 penetrates a center of a nozzle main body 10and can be seen at the center of the end portion. The liquid flows outof the hole 2, spreads over the grooves 5, and further spreads over theentire plane through the concave-convex portions 3.

This nozzle was attached to a polyethylene container (see FIG. 3), 0.1 gof LIMUVEIL HV (1.2% fucoidan-containing aqueous solution, manufacturedby TANGLEWOOD) was dissolved in 200 g of water, and thefucoidan-containing extract was charged in the container to prepare anapplicator.

The microneedle patch was manufactured as follows. To 90 g of water, 5 gof hyaluronic acid (FCH-80, originating from culture, manufactured byKikkoman Biochemifa Company) and 5 g of LIMUVEIL HV were added, toprepare a homogeneous solution. The aqueous solution was cast on a mold,dried at room temperature for 24 hours, and removed from the mold toobtain a microneedle array sheet. The sheet was cut into a microneedlearray having a diameter of 1 cm. A fucoidan content per one microneedlewas 25 μg. This microneedle patch and the extract are preparationsintended for hair growth.

Prior to use, the back side of the microneedle array was pressed, pastedand held by the applicator nozzle portion. The array was pressed againsta forehead of a volunteer, and the container was pushed to supply thefucoidan extract from the back side of the microneedle array. When theapplicator was removed after 1.5 minutes, the microneedle array wasdissolved on the skin. The microneedle array sheet did not remain in theapplicator nozzle portion.

In a case of a microneedle array containing a hair grower, anapplication site has hairs, and thus the array hardly adheres to theskin only by press with a finger or the like. Using the applicatoraccording to the present invention, the microneedle array rapidlydissolves (in a very short time) while pressing the microneedle arrayagainst the skin. The microneedle array is pressed by the applicatoruntil the array dissolves, so that the hair grower can be reliablydelivered into the skin.

Comparative Example 1

The same test as in Example 1 was carried out using a nozzle having aflat bottom surface without concaves and convexes (the outer shape isthe same as in Example 1). The fucoidan extract was supplied from theback side of the microneedle array by pushing the container. When theapplicator was removed after 1.5 minutes, the microneedle array adheredto the bottom surface of the nozzle, furthermore the bottom surfacecould not be uniformly wetted by water, and therefore the microneedlearray insufficiently dissolved.

Comparative Example 2

The microneedle array was pasted to a forehead of a volunteer, then theback side of the array was covered with a medical tape to hold the arrayon the skin. In this case, it took 3 hours to dissolve the needleportion.

REFERENCE NUMERALS

-   1 end portion of nozzle-   2 hole-   3 concave-convex portion-   4 convex portion on peripheral edge-   5 groove-   10 nozzle main body-   20 liquid container-   21 opening of liquid container-   22 pump-   23 spray device

1. A nozzle having at least one hole on an end portion having a planewith a size capable of holding a sheet-like water-soluble preparation,and having concave-convex portions on a portion of the plane excludingthe hole.
 2. The nozzle according to claim 1, wherein a depth of theconcave-convex portions is 0.1 to 3.0 mm.
 3. The nozzle according toclaim 1, wherein the concave-convex portions form grooves extending fromthe hole toward a peripheral edge of the end portion.
 4. The nozzleaccording to claim 1, wherein the peripheral edge of the end portion issurrounded by a convex portion higher than the concave-convex portions.5. The nozzle according to claim 1, wherein the nozzle is made of asynthetic resin selected from a group consisting of a polyethyleneresin, a polypropylene resin, a polyurethane resin, a polyvinylchloride, and a silicone resin.
 6. An applicator for a sheet-likewater-soluble preparation, wherein the applicator is composed of aliquid container and the nozzle according to claim
 1. 7. The applicatoraccording to claim 6, wherein the nozzle is attached to an opening ofthe liquid container.
 8. The applicator according to claim 6, whereinthe sheet-like water-soluble preparation is held on the end portion ofthe nozzle so as to be applied to the skin, and a liquid is supplied toa back side of the preparation by pressing the liquid container.
 9. Theapplicator according to claim 6, wherein the liquid container isequipped with a spray device, and the nozzle is attached to an endopening of the spray device.
 10. The applicator according to claim 9,wherein the sheet-like water-soluble preparation is held on the endportion of the nozzle so as to be applied to the skin, and the liquid issupplied to the back side of the preparation by discharge from the spraydevice.
 11. The applicator according to claim 6, wherein the liquidcontainer is equipped with a pump, and the nozzle is attached to an endopening of the pump.
 12. The applicator according to claim 11, whereinthe sheet-like water-soluble preparation is held on the end portion ofthe nozzle so as to be applied to the skin, and the liquid is ejected tothe back side of the preparation by pushing the pump.